[unreadable] This Phase I SBIR application is presented by Aeris Therapeutics, Inc. of Woburn, MA. It will examine the feasibility of using a novel enzyme based-system to produce safe, clinically-effective pleurodesis for treatment of malignant pleural effusions. Preliminary data, summarized in this application, suggest that an enzymatic system has the potential for being safer, simpler, less expensive, and more effective than existing treatment strategies. Pleural symphysis, wherein the visceral and parietal pleural surfaces become "fused," is essential for achieving clinically effective pleurodesis. This is most effectively accomplished by surgical stripping of the parietal pleura, which is followed by adherence of the visceral surface to the inner chest wall during healing. Aeris' enzyme based pleurodesis system replicates the effects of surgical pleurectomy without requiring surgery, using a buffered solution of trypsin and collagenase that chemically strips away the parietal and visceral pleural surfaces, leading to pleural symphysis and elimination of pleural effusions. In preliminary studies conducted in healthy sheep, this approach produced safe and effective pleurodesis within 21 days of treatment without clinical toxicity, altered lung physiology, or histological injury to lung parenchyma or soft tissue of the chest wall. The current proposal will focus on: 1) optimizing enzyme concentrations in the formulation to maximize safety and effectiveness in vivo, and 2) comparing responses following enzymatic treatment to those following talc slurry, the current standard non-surgical treatment for malignant effusions in clinical practice. [unreadable] [unreadable] [unreadable]